16-1678326-C-T

Variant names:

• chr16-1678326-C-T
• rs777033509
• NM_144570.3:c.14C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144570.3(JPT2):​c.14C>T​(p.Pro5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,084,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P5R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: JPT2 NM_144570.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

Genes affected

JPT2 (HGNC:14137): (Jupiter microtubule associated homolog 2) Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261732 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04760638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144570.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPT2	NM_144570.3	MANE Select	c.14C>T	p.Pro5Leu	missense	Exon 1 of 5	NP_653171.1	Q9H910-1
	JPT2	NM_001434664.1		c.14C>T	p.Pro5Leu	missense	Exon 1 of 7	NP_001421593.1
	JPT2	NM_001434665.1		c.14C>T	p.Pro5Leu	missense	Exon 1 of 6	NP_001421594.1	Q9H910-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPT2	ENST00000248098.8	TSL:1 MANE Select	c.14C>T	p.Pro5Leu	missense	Exon 1 of 5	ENSP00000248098.3	Q9H910-1
	JPT2	ENST00000561516.5	TSL:1	c.14C>T	p.Pro5Leu	missense	Exon 1 of 4	ENSP00000454459.1	H3BMM8
	JPT2	ENST00000569256.5	TSL:1	n.71C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1084640 Hom.: 0 Cov.: 32 AF XY: 0.00000195 AC XY: 1 AN XY: 512746

African (AFR) AF: 0.00 AC: 0 AN: 22760

American (AMR) AF: 0.00 AC: 0 AN: 8796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14190

East Asian (EAS) AF: 0.00 AC: 0 AN: 26312

South Asian (SAS) AF: 0.00 AC: 0 AN: 19682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3634

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 919380

Other (OTH) AF: 0.0000230 AC: 1 AN: 43526

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	10
DANN	Benign	0.86
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.072
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.062
MutPred		0.29		Gain of sheet (P = 0.0043)
MVP		0.043
MPC		0.50
ClinPred		0.045	T
GERP RS		-0.047
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.15
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs777033509; hg19: chr16-1728327;